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P32019 (I5P2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Type II inositol 1,4,5-trisphosphate 5-phosphatase

EC=3.1.3.36
Alternative name(s):
75 kDa inositol polyphosphate-5-phosphatase
Phosphoinositide 5-phosphatase
Short name=5PTase
Gene names
Name:INPP5B
Synonyms:OCRL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length993 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. Ref.1

Catalytic activity

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate. Ref.1

Subunit structure

Interacts with APPL1, FAM109A and FAM109B. Interacts with several Rab GTPases, at least RAB1A, RAB2A, RAB5A, RAB6A, RAB8A, RAB9A and RAB33B; these interactions may play a dual role in targeting INPP5B to the specific membranes and stimulating the phosphatase activity. Ref.6 Ref.7 Ref.9

Subcellular location

Cytoplasmcytosol. Endoplasmic reticulum-Golgi intermediate compartment. Early endosome membrane. Membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesiclephagosome membrane By similarity. Golgi apparatus Ref.1 Ref.6.

Tissue specificity

Platelets.

Domain

The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by FAM109A and FAM109B as endosomes mature, all three interactions relie on F&H motifs, an approximately 12-13 amino-acid sequence centered around Phe and His residues essential for binding By similarity.

Post-translational modification

Isoprenylation at Cys-990 may be required for localization at the membrane.

May be proteolytically cleaved after Lys-320 as inferred from N-terminal protein sequence of the 75 kda form (Ref.5).

Sequence similarities

Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.

Contains 1 PH domain.

Contains 1 Rho-GAP domain.

Sequence caution

The sequence AAA79207.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoplasmic vesicle
Endosome
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMagnesium
Metal-binding
   Molecular functionHydrolase
   PTMLipoprotein
Methylation
Prenylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processin utero embryonic development

Inferred from electronic annotation. Source: Ensembl

inositol phosphate metabolic process

Traceable author statement. Source: Reactome

phosphatidylinositol dephosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

regulation of protein processing

Inferred from electronic annotation. Source: Ensembl

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

sperm motility

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Inferred from direct assay Ref.1. Source: UniProtKB

early endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum-Golgi intermediate compartment

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from direct assay Ref.1. Source: UniProtKB

microtubule cytoskeleton

Inferred from direct assay. Source: HPA

phagocytic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioninositol-1,4,5-trisphosphate 5-phosphatase activity

Inferred from direct assay Ref.1. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity

Inferred from direct assay Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P32019-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: No experimental confirmation available.
Isoform 2 (identifier: P32019-2)

The sequence of this isoform differs from the canonical sequence as follows:
     178-257: Missing.
Isoform 3 (identifier: P32019-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-244: Missing.
Isoform 4 (identifier: P32019-4)

The sequence of this isoform differs from the canonical sequence as follows:
     810-828: TLMPVWTGDDGSQLDSPME → LAYLAAYCFETQLVTKSLI
     829-993: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 990990Type II inositol 1,4,5-trisphosphate 5-phosphatase
PRO_0000015640
Propeptide991 – 9933Removed in mature form Potential
PRO_0000422293

Regions

Domain22 – 148127PH
Domain821 – 993173Rho-GAP
Region342 – 6683275-phosphatase By similarity
Region459 – 4602Substrate binding
Region582 – 5832Substrate binding
Region596 – 5983Substrate binding
Region669 – 782114ASH By similarity

Sites

Metal binding3551Magnesium
Metal binding3831Magnesium
Binding site3831Substrate

Amino acid modifications

Modified residue9901Cysteine methyl ester Potential
Lipidation9901S-farnesyl cysteine Potential

Natural variations

Alternative sequence1 – 244244Missing in isoform 3.
VSP_012821
Alternative sequence178 – 25780Missing in isoform 2.
VSP_012820
Alternative sequence810 – 82819TLMPV…DSPME → LAYLAAYCFETQLVTKSLI in isoform 4.
VSP_013902
Alternative sequence829 – 993165Missing in isoform 4.
VSP_013903
Natural variant461G → S.
Corresponds to variant rs56993041 [ dbSNP | Ensembl ].
VAR_061270
Natural variant7451M → T. Ref.1 Ref.3 Ref.5
Corresponds to variant rs11488569 [ dbSNP | Ensembl ].
VAR_028002

Experimental info

Mutagenesis9901C → S: Loss of prenylation and membrane localization. Ref.1
Sequence conflict587 – 60620GSDDW…WCDRI → RALTTGIPVRSAVLLPGVIG F AA sequence Ref.5
Sequence conflict9111G → P AA sequence Ref.5

Secondary structure

............................................. 993
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 15, 2009. Version 4.
Checksum: ABD3581CC6CD29D6

FASTA993112,852
        10         20         30         40         50         60 
MDQSVAIQET LAEGEYCVIA VQGVLCEGDS RQSRLLGLVR YRLEHGGQEH ALFLYTHRRM 

        70         80         90        100        110        120 
AITGDDVSLD QIVPVSRDFT LEEVSPDGEL YILGSDVTVQ LDTAELSLVF QLPFGSQTRM 

       130        140        150        160        170        180 
FLHEVARACP GFDSATRDPE FLWLSRYRCA ELELEMPTPR GCNSALVTWP GYATIGGGRY 

       190        200        210        220        230        240 
PSRKKRWGLE EARPQGAGSV LFWGGAMEKT GFRLMERAHG GGFVWGRSAR DGRRDEELEE 

       250        260        270        280        290        300 
AGREMSAAAG SRERNTAGGS NFDGLRPNGK GVPMDQSSRG QDKPESLQPR QNKSKSEITD 

       310        320        330        340        350        360 
MVRSSTITVS DKAHILSMQK FGLRDTIVKS HLLQKEEDYT YIQNFRFFAG TYNVNGQSPK 

       370        380        390        400        410        420 
ECLRLWLSNG IQAPDVYCVG FQELDLSKEA FFFHDTPKEE EWFKAVSEGL HPDAKYAKVK 

       430        440        450        460        470        480 
LIRLVGIMLL LYVKQEHAAY ISEVEAETVG TGIMGRMGNK GGVAIRFQFH NTSICVVNSH 

       490        500        510        520        530        540 
LAAHIEEYER RNQDYKDICS RMQFCQPDPS LPPLTISNHD VILWLGDLNY RIEELDVEKV 

       550        560        570        580        590        600 
KKLIEEKDFQ MLYAYDQLKI QVAAKTVFEG FTEGELTFQP TYKYDTGSDD WDTSEKCRAP 

       610        620        630        640        650        660 
AWCDRILWKG KNITQLSYQS HMALKTSDHK PVSSVFDIGV RVVNDELYRK TLEEIVRSLD 

       670        680        690        700        710        720 
KMENANIPSV SLSKREFCFQ NVKYMQLKVE SFTIHNGQVP CHFEFINKPD EESYCKQWLN 

       730        740        750        760        770        780 
ANPSRGFLLP DSDVEIDLEL FVNKMTATKL NSGEDKIEDI LVLHLDRGKD YFLSVSGNYL 

       790        800        810        820        830        840 
PSCFGSPIHT LCYMREPILD LPLETISELT LMPVWTGDDG SQLDSPMEIP KELWMMVDYL 

       850        860        870        880        890        900 
YRNAVQQEDL FQQPGLRSEF EHIRDCLDTG MIDNLSASNH SVAEALLLFL ESLPEPVICY 

       910        920        930        940        950        960 
STYHNCLECS GNYTASKQVI STLPIFHKNV FHYLMAFLRE LLKNSAKNHL DENILASIFG 

       970        980        990 
SLLLRNPAGH QKLDMTEKKK AQEFIHQFLC NPL 

« Hide

Isoform 2 [UniParc].

Checksum: 4882C26F6E4DC9C6
Show »

FASTA913103,987
Isoform 3 [UniParc].

Checksum: 50921FAACF7E1E39
Show »

FASTA74985,620
Isoform 4 [UniParc].

Checksum: 9CD5C12DCF509A50
Show »

FASTA82893,924

References

« Hide 'large scale' references
[1]"Properties of type II inositol polyphosphate 5-phosphatase."
Jefferson A.B., Majerus P.W.
J. Biol. Chem. 270:9370-9377(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-990, MUTAGENESIS OF CYS-990, VARIANT THR-745.
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), VARIANT THR-745.
Tissue: Lymph.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-178.
Tissue: Stomach.
[5]"Cloning and expression of human 75-kDa inositol polyphosphate-5-phosphatase."
Ross T.S., Jefferson A.B., Mitchell C.A., Majerus P.W.
J. Biol. Chem. 266:20283-20289(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 284-954, PROTEIN SEQUENCE OF 321-339, VARIANT THR-745.
Tissue: Placenta.
[6]"Targeting of the type II inositol polyphosphate 5-phosphatase INPP5B to the early secretory pathway."
Williams C., Choudhury R., McKenzie E., Lowe M.
J. Cell Sci. 120:3941-3951(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH RAB GTPASES.
[7]"Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1."
Swan L.E., Tomasini L., Pirruccello M., Lunardi J., De Camilli P.
Proc. Natl. Acad. Sci. U.S.A. 107:3511-3516(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAM109A.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway."
Noakes C.J., Lee G., Lowe M.
Mol. Biol. Cell 22:606-623(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAM109A AND FAM109B.
[10]"Crystal structure of INPP5B in complex with phosphatidylinositol 4-phosphate (CASP target)."
Structural genomics consortium (SGC)
Submitted (JUL-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 339-646 IN COMPLEX WITH MAGNESIUM AND PHOSPHATIDYLINOSITOL 4-PHOSPHATE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M74161 mRNA. Translation: AAA79207.1. Different initiation.
AL603790, AL929472 Genomic DNA. Translation: CAH69926.1.
AL603790, AL929472 Genomic DNA. Translation: CAH69928.1.
AL603790, AL929472 Genomic DNA. Translation: CAH69929.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70076.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70079.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70080.1.
BX296560 Genomic DNA. No translation available.
BC042529 mRNA. Translation: AAH42529.2.
BC058932 mRNA. Translation: AAH58932.1.
AL833055 mRNA. Translation: CAH56301.1.
CCDSCCDS41306.1. [P32019-2]
RefSeqNP_005531.2. NM_005540.2. [P32019-2]
XP_005270893.1. XM_005270836.1. [P32019-3]
UniGeneHs.449942.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3MTCX-ray2.40A339-643[»]
3N9VX-ray2.65A/B342-646[»]
4CMLX-ray2.30A339-643[»]
ProteinModelPortalP32019.
SMRP32019. Positions 1-155, 339-643, 656-989.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109845. 2 interactions.
STRING9606.ENSP00000362115.

PTM databases

PhosphoSiteP32019.

Polymorphism databases

DMDM281185510.

Proteomic databases

MaxQBP32019.
PaxDbP32019.
PRIDEP32019.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373023; ENSP00000362114; ENSG00000204084. [P32019-1]
ENST00000373024; ENSP00000362115; ENSG00000204084. [P32019-2]
ENST00000373026; ENSP00000362117; ENSG00000204084. [P32019-1]
ENST00000373027; ENSP00000362118; ENSG00000204084. [P32019-3]
GeneID3633.
KEGGhsa:3633.
UCSCuc001ccf.1. human. [P32019-1]
uc001ccg.1. human. [P32019-2]

Organism-specific databases

CTD3633.
GeneCardsGC01M038326.
HGNCHGNC:6077. INPP5B.
HPAHPA028803.
MIM147264. gene.
neXtProtNX_P32019.
PharmGKBPA29885.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5411.
HOVERGENHBG000070.
InParanoidP32019.
KOK01099.
OMAPMEIPKE.
OrthoDBEOG7J4465.
PhylomeDBP32019.
TreeFamTF317034.

Enzyme and pathway databases

BioCycMetaCyc:HS05898-MONOMER.
BRENDA3.1.3.36. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
SABIO-RKP32019.

Gene expression databases

ArrayExpressP32019.
BgeeP32019.
CleanExHS_INPP5B.
GenevestigatorP32019.

Family and domain databases

Gene3D1.10.555.10. 1 hit.
3.60.10.10. 1 hit.
InterProIPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
[Graphical view]
PfamPF03372. Exo_endo_phos. 1 hit.
PF00620. RhoGAP. 1 hit.
[Graphical view]
SMARTSM00128. IPPc. 1 hit.
SM00324. RhoGAP. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 2 hits.
SSF56219. SSF56219. 1 hit.
PROSITEPS50238. RHOGAP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSINPP5B. human.
EvolutionaryTraceP32019.
GeneWikiINPP5B.
GenomeRNAi3633.
NextBio14219.
PROP32019.
SOURCESearch...

Entry information

Entry nameI5P2_HUMAN
AccessionPrimary (citable) accession number: P32019
Secondary accession number(s): C9J6U5 expand/collapse secondary AC list , Q5VSG9, Q5VSH0, Q5VSH1, Q658Q5, Q6P6D4, Q6PD53, Q86YE1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: December 15, 2009
Last modified: July 9, 2014
This is version 135 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM